In the article "Multispecific drugs herald a new era of biopharmaceutical innovation" published today in Nature, Raymond Deshaies, Ph.D., senior vice president of Global Research at Amgen, discusses how the advent of multispecific drugs is leading the next revolution of drug discovery and development. In the review, Deshaies describes the major classes of multispecific drugs and how they work, provides a perspective on what the future holds, and discusses challenges that must be overcome to make the coming wave of transformative innovation a reality.
Instead of engaging targets on their own like conventional medicines, one class of multispecific drugs tethers the active agent at its intended site of action, whereas a second class mobilizes biological mechanisms to do the heavy lifting. These latter agents bring two things together, like a molecular matchmaker. On one end the drug binds to the target to be altered (inhibited, activated or destroyed) and the other end binds to the cellular effector that acts on the target. Matchmaker multispecific drugs have the potential to target the 85% of proteins currently thought of as "undruggable."
"In the future medicines could function very differently than conventional medicines do today. In biopharma pipelines across the industry, we're seeing more and more multispecific drugs that can form connections with two or more proteins," said Deshaies. "They include some highly sophisticated structures that function as molecular matchmakers. By inducing proximity between their targets and natural enzymes or even cells, multispecifics can harness the awesome power of biology to go well beyond what conventional drugs can accomplish. This isn't an incremental improvement in drug design, it's a sea change."
There are many versatile natural mechanisms that induced proximity medicines can use to fight disease when matched with the right target, and Amgen is at the forefront with its Bispecific T-cell engager (BiTE®) molecules and Induced Proximity Platform (IPP). Approximately two-thirds of Amgen's pipeline molecules through Phase 1 are multispecifics.
Amgen has experience building highly promising platform technologies. In 2012, Amgen acquired Micromet, which pioneered the BiTE® technology platform to develop BiTE® molecules. BiTE® molecules work by inducing proximity at the cellular level by bringing T cells together with tumor cells so the T cells can recognize and destroy the tumor cells. Amgen is exploring other areas of induced proximity including PROTAC® (proteolysis targeting chimeras) molecules, which leverage the enzymes that tag unwanted or damaged proteins for destruction by a molecular machine called the proteasome.
Visit http://www.AmgenScience.com to read an editorial by Dr. Deshaies and learn more about Amgen's approach to multispecific medicines with the IPP.
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
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